How to Study Placebo Responses in Motion Sickness with a Rotation Chair Paradigm in Healthy Participants
December 14th, 2014
An experimental rotation chair paradigm is used to investigate whether a placebo intervention on motion sickness affects subjective outcome measures only or also affects behavioral and objective measures in a balanced placebo design.
The overall goal of this procedure is to investigate whether a placebo intervention on motion sickness affects subjective outcome measures only, or also affects behavioral and objective measures. This is accomplished by using a balanced placebo design with a rotation chair paradigm in the balanced placebo design, BPD for short. The study group is divided into four subgroups.
Half of the participants receive the real drug and the other half receives a placebo. Half of the participants of each drug group receive the correct information and the other half receives the wrong information about the drug received. With the BPD, we can investigate the effects of a drug compared to a placebo and the effects of expectations by verbal information before and after the rotation procedures.
The participants are asked to rate a list of subjective symptoms that typically occurred during motion sickness, such as vertigo, nausea, or headache. Ideally, the rotation procedure consists of five runs of two minutes each with one minute breaks in between behavioral measures, such as the number of head movements and the total rotation time tolerated are assessed. The gastric myoelectrical activity is objectively recorded with electric gastroscopy, EGG.
After the rotation procedure, the outcome variables are calculated. The EGG data is screened and analyzed to detect shifts from normal gastra to tachy gastra. Prepare the drugs used a table to fill in rotation times and the number of head movements during the runs of the rotation Procedure.
A questionnaire to fill in the symptom ratings of the participant headphones and an eye mask. Prepare the equipment for recording the EGG cutaneous electrodes, the EGG device with fero technology and a stopwatch to assess rotation times. Place three cutaneous electrodes on the skin above the stomach of the participant.
Place the first electrode on the lower third of the midline between the umbilicus and sternum. Place the second electrode in a 45 degree angle, upwards from the first electrode, but under the lowest drip on the left side. Place the third electrode, the reference electrode in a 45 degree angle downwards from the first electrode to the right side.
Connect the electrodes to the EGG device seat the participant in the rotation chair. Start the recording software and store the EGG device in a bag at the backside of the chair. This is important to prevent the cables from getting entangled.
The first baseline assessment is taken before drug intake record at least 15 minutes of EGG previous to any intervention. Instruct the participant not to move, speak, or take deep breaths during this period of time. According to group assignment, the participant takes the pills, drug or placebo without receiving any information about their content.
The second baseline assessment is taken after drug intake record at least 15 minutes of EGG after drug intake. Instruct the participant not to move, speak, or take deep breaths during this period of time. Afterwards, ask the participant for seven symptoms of motion sickness on a scale between zero, no symptom to five severe symptom.
The symptoms are vertigo, headache, nausea, urge to vomit, tiredness, sweating, and stomach awareness immediately before the rotation. Procedure informed the participant about his group assignment according to the balanced placebo design. That is if he received the real drug or the placebo.
Instruct the participant to Move his head up and down when he hears the beep tone from the earphones. Participants should not vomit during the procedure and can skip head movements or tell the experimenter to stop the rotation at any time. If they strongly feel an urge to vomit, the participant will wear an eye mask and earphones and hear a beep every 10 seconds.
Confirm that the participant is ready to begin, then start the rotation procedure. The rotation procedure consists of five, runs each with two minutes of rotation at a constant speed of 120 degrees per second and a one minute break in between the runs. Count the head movements right after The rotation procedure.
Note the rotation time of the run and the number of head movements immediately after. Ask the participant to rate the seven symptoms from zero to five. Note the rating on the questionnaire.
If the participant does not object, repeat the process five times in order to get comparable results. It is important to stick to the same interval of runs and breaks after the last run is finished and the subjective symptoms have been rated. Record another 15 minutes of EGG during which participants should not move.
Speak or take deep breaths. Calculate subjective symptom ratings by adding the scores of each symptom for each of the six time points at baseline. And after each run separately, calculate the maximum symptom rating.
Add up rotation times for the total rotation tolerance in seconds. Add the number of head movements during the rotation procedure for the total Number of head movements. Visually screen the Raw EGG data for artifacts and select at least five minutes of artifact free recording during the recording periods.
As a rule of thumb, artifacts are defined as signals with fast and sudden onset and signals stronger than a thousand microvolt. Because such signals are improbable gastric myoelectrical activities, use a fast four year transformation software to analyze the frequency domain of the EGG signal. Calculate the percentage spectral power of the normal gastra and tachy gastra bands from the total range and compute the EGG ratio.
A shift towards tachy gastra that is a decreasing ratio, has repeatedly been associated with nausea in motion sickness induced by rotation chair or EV action Drum. The conducted study Showed that the information given did not significantly affect the EGG ratio, but results provide hints that the information could have had some effect as the placebo group had the lowest EGG ratio and the ginger group had the highest EDG ratio. Yeah, the main results of this study was in this balanced placebo design that we found no main effect of ginger or placebo, but we found an interaction effect with the gender of the experimenters and the participants.
So in male participants, we found an effect when they got the ginger information, when it was given by the female experimenter. So this was a really interaction effect here. The main advantage of this method is that we have different kind of measures.
We have a very objective measure, the EGG, the electro gastric gastro gram, but also subjective measures. This method thus provides the possibility to assess the main and interactional effects of drug and information, as well as the multivariate assessment of placebo Responses.
Overview
This study investigates the effects of a placebo intervention on motion sickness using a rotation chair paradigm. The research aims to determine if the placebo affects only subjective measures or also behavioral and objective outcomes.
Key Study Components
Area of Science
- Neuroscience
- Psychology
- Pharmacology
Background
- Motion sickness is a common condition affecting many individuals.
- Placebo interventions can influence subjective experiences and physiological responses.
- A balanced placebo design allows for the assessment of both drug effects and expectation effects.
- Understanding these effects can enhance treatment strategies for motion sickness.
Purpose of Study
- To evaluate the impact of a placebo on subjective symptoms of motion sickness.
- To assess whether the placebo also influences behavioral and objective measures.
- To utilize a balanced placebo design to differentiate between drug effects and expectation effects.
Methods Used
- Participants are divided into four subgroups receiving either a drug or placebo with varying information about their treatment.
- Subjective symptoms are rated on a scale before and after a series of rotation runs.
- Behavioral measures, such as head movements and rotation tolerance, are recorded.
- Gastric myoelectrical activity is monitored using electric gastroscopy (EGG) to provide objective data.
Main Results
- The study found no significant effect of information on the EGG ratio.
- However, the placebo group exhibited the lowest EGG ratio, suggesting potential effects of expectation.
- Results indicate that the ginger group had the highest EGG ratio, hinting at varying responses to interventions.
- Subjective symptom ratings varied across the different groups, reflecting the influence of both drug and placebo.
Conclusions
- The findings suggest that placebos can influence both subjective and objective measures of motion sickness.
- Further research is needed to explore the mechanisms behind these effects.
- Understanding the role of expectation in treatment can improve therapeutic approaches for motion sickness.
Frequently Asked Questions
Executive Industry Relevance
Understanding placebo responses in motion sickness requires multivariate assessment of subjective, behavioral, and objective physiological measures. This approach enables de-risking of target validation by distinguishing drug-specific effects from expectation-driven responses in early discovery. The rotation chair paradigm with electrogastrography provides a disease-relevant system to evaluate mechanistic pathways underlying nausea and vertigo.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Interrogates therapeutic hypotheses by isolating drug effects from expectation effects using balanced placebo design.
- Operational Value: Enables functional target validation through multivariate symptom assessment across subjective, behavioral, and gastric myoelectrical domains.
- Predictive Value: Supports portfolio triage by quantifying placebo contribution to outcome variability in motion sickness models.
Screening & Assay Development
- Scientific Value: Prepares validated biological systems for downstream screening by establishing baseline gastric myoelectrical activity profiles.
- Operational Value: Standardizes assay reproducibility through controlled rotation chair parameters and EGG signal processing protocols.
- Scalability: Supports platform reuse for evaluating anti-motion sickness compounds via quantifiable EGG ratio shifts.
Translational & Preclinical Research
- Scientific Value: Aligns with disease relevance by targeting gastric tachyarrhythmia as a physiological correlate of motion sickness.
- Operational Value: Ensures translational continuity from discovery through preclinical validation using objective EGG readouts.
- Risk Mitigation: Informs risk-adjusted advancement decisions by identifying expectation-driven confounders in efficacy assessments.
Pipeline & Workflow Integration
The method integrates into early discovery workflows by enabling hypothesis testing of anti-motion sickness compounds while controlling for expectation biases through balanced placebo design.
- Discovery Biology: Supports pathway clarification by measuring shifts in gastric myoelectrical activity from normogastria to tachygastria as a biomarker of motion sickness susceptibility.
- Screening: Delivers assay readiness through standardized EGG artifact screening and frequency-domain analysis using fast Fourier transformation.
- Analytics: Provides quantitative EGG ratio outputs that enable cross-condition comparison of drug and information effects on gastric motility.
- Translational Research: Connects to preclinical continuity by validating gastric myoelectrical activity as a translational biomarker for motion sickness severity.
- Enterprise Reuse: Functions as a reusable capability for evaluating CNS-acting compounds where expectation effects may confound efficacy readouts.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence by de-risking mechanistic ambiguity between pharmacological and expectation-driven responses.
- Operational Value: Enhances standardization and reproducibility through defined electrode placement, rotation parameters, and EGG signal processing thresholds.
- Strategic Value: Improves go/no-go decisions by isolating true drug effects from placebo-mediated behavioral and physiological changes.
- Portfolio Impact: Enables risk-adjusted prioritization by quantifying placebo contribution to outcome variance in motion sickness models.
Implementation Considerations
- Requires expertise in electrogastrography signal acquisition and artifact identification.
- Dependent on instrumentation capable of recording cutaneous EGG signals with microvolt sensitivity.
- Necessitates cross-team standardization of balanced placebo design procedures across behavioral and physiological measurement teams.
- Involves adaptation considerations when applying the paradigm to different motion sickness inducers beyond rotation chair.
- Limited by the need to identify appropriate physiological correlates for target organ engagement in placebo response studies.
